This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The research focuses on the nuclear hormone family of proteins. Nuclear hormone receptor proteins are ligand inducible transcription factors. Nuclear hormone receptors are involved in several human diseases including cancer, liver disease, obesity, and diabetes. Specifically, we are working with the ligand binding domains of estrogen receptor alpha (ERalpha LBD) and peroxisome proliferator activated receptor gamma (PPAR-gamma). Our goal is to acquire a better understanding of the partial agonism mechanism of these proteins in order to carry out structure based drug design. Experimentally, we desire to characterize several partial agonists bound to PPAR and ER, solve the structures by x-ray crystallography, dissect the atomic level interactions of the ligands, and compare and contrast these interactions and induced allostery with full agonists and antagonists.